The administration of angiogenic growth factors has been proposed for treatment of ischemic heart disease. It appears that therapeutic angiogenesis is best derived from low-level, long duration secretion of these factors., making gene transfer an appealing delivery strategy. However, concerns with current vector t3echnology and the inability to regulated gene expression have hampered clinical development of this approach. Although recent suggest that in vivo electroporation is capable of efficient and consistent gene delivery in various tissues, its potential utility for myocardial gene transfer has yet to be assessed. Ichor has already developed electroporation technology for drug and gene delivery in other tissues, the company is well positioned to adapt the technique for application in the heart. If successful, electroporation could enable consistent and effective delivery of angiogenic growth factor genes into ischemic myocardium. During Phase I, Ichor will demonstrate basic feasibility of Electroporation mediated gene delivery in cardiac tissue. The scope of the research includes adaptation of electroporation for cardiac application, assessment of safety and efficacy in small animal models, and evaluation of a novel expression regulation strategy. Successful completion of Phase I will lead to further testing in large animals and development of equipment suitable for clinical application. PROPOSED COMMERCIAL APPLICATIONS: Unlike other non-viral methods of gene transfer, electroporation appears to be capable of reliably achieving high levels of gene expression. Although potentially applicable for a variety of gene transfer strategies in cardiac tissue, the delivery of genes encoding angiogenic growth factors represents the most appropriate application for initial investigation. Based on previous experience in other tissues, it appears electroporation has the potential to significantly increase dosing consistency while reducing the DNA dose and volume of injection required to achieve therapeutic effect. Initial indications for this procedures would include patients with intractable coronary artery disease, for whom there are few treatment options.